Recurrent Gleason Score 6 Prostate Cancer After Radiotherapy or Ablation: Should We Observe Them All? Results from a Large Multicenter Salvage Radical Prostatectomy Consortium

Giancarlo Marra; Giorgio Calleris; Francesca Conte; Nicole Benfant; Pawel Rajwa; Mohamed Ahmed; Andre Abreu; Giovanni Cacciamani; Joseph A Smith; Steven Joniau; Lara Rodriguez-Sanchez; Rafael Sanchez-Salas; Paul Cathcart; Inderbir Gill; Robert Jeffrey Karnes; Derya Tilki; Shahrokh F Shariat; Karim Touijer; Paolo Gontero

doi:10.1016/j.euf.2023.08.007

Recurrent Gleason Score 6 Prostate Cancer After Radiotherapy or Ablation: Should We Observe Them All? Results from a Large Multicenter Salvage Radical Prostatectomy Consortium

Eur Urol Focus. 2023 Sep 11:S2405-4569(23)00194-3. doi: 10.1016/j.euf.2023.08.007. Online ahead of print.

Authors

Giancarlo Marra¹, Giorgio Calleris², Francesca Conte¹, Nicole Benfant³, Pawel Rajwa⁴, Mohamed Ahmed⁵, Andre Abreu⁶, Giovanni Cacciamani⁶, Joseph A Smith⁷, Steven Joniau⁸, Lara Rodriguez-Sanchez⁹, Rafael Sanchez-Salas⁹, Paul Cathcart¹⁰, Inderbir Gill⁶, Robert Jeffrey Karnes⁵, Derya Tilki¹¹, Shahrokh F Shariat¹², Karim Touijer³, Paolo Gontero¹

Affiliations

¹ Department of Surgical Sciences and Urology Clinic, University of Turin and Città della Salute e della Scienza, Turin, Italy.
² Department of Surgical Sciences and Urology Clinic, University of Turin and Città della Salute e della Scienza, Turin, Italy. Electronic address: giorgio.calleris@unito.it.
³ Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
⁴ Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
⁵ Department of Urology, Mayo Clinic, Rochester, MN, USA.
⁶ USC Institute of Urology & The Catherine and Joseph Aresty Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
⁷ Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.
⁸ Department of Urology, University Hospitals Leuven, Leuven, Belgium.
⁹ Department of Urology, Institut Mutualiste Montsouris and Université Paris Descartes, Paris, France.
¹⁰ Urology Centre, Guy's Hospital, London, UK.
¹¹ Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany; Department of Urology, University Hospital Hamburg-Eppendorf, Hamburg, Germany; Department of Urology, Koc University Hospital, Istanbul, Turkey.
¹² Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Departments of Urology, Weill Cornell Medical College, New York, New York, USA; Department of Urology, University of Texas Southwestern, Dallas, Texas, USA; Research Center for Evidence-Based Medicine, Iranian EBM Center: A Joanna Briggs Institute Center of Excellence, Tabriz University of Medical Sciences, Tabriz, Iran; Division of Urology, Department of Special Surgery, Jordan University Hospital, The University of Jordan, Amman, Jordan.

PMID: 37704503
DOI: 10.1016/j.euf.2023.08.007

Abstract

Background: Salvage radical prostatectomy (sRP) yields poor functional outcomes and relatively high complication rates. Gleason score (GS) 6 prostate cancer (PCa) has genetic and clinical features showing little, if not absent, metastatic potential. However, the behavior of GS 6 PCa recurring after previous PCa treatment including radiotherapy and/or ablation has not been investigated.

Objective: To evaluate the oncological outcomes of sRP for radio- and/or ablation-recurrent GS 6 PCa.

Design, setting, and participants: Retrospective data of sRP for recurrent PCa after local nonsurgical treatment were collected from 14 tertiary referral centers from 2000 to 2021.

Intervention: Prostate biopsy before sRP and sRP.

Outcome measurements and statistical analysis: A survival analysis was performed for pre-sRP biopsy and sRP-proven GS 6. Concordance between PCa at pre-sRP biopsy and sRP histology was assessed.

Results and limitations: We included GS 6 recurrent PCa at pre-sRP biopsy (n = 142) and at sRP (n = 50), as two cohorts. The majority had primary radiotherapy and/or brachytherapy (83.8% of GS 6 patients at pre-sRP biopsy; 78% of GS 6 patients at sRP) and whole-gland treatments (91% biopsy; 85.1% sRP). Biopsy GS 6 10-yr metastasis, cancer-specific survival (CSS), and overall survival (OS) were 79% (95% confidence interval [CI] 61-89%), 98% (95-99%), and 89% (78-95%), respectively. Upgrading at sRP was 69%, 35.5% had a pT3 stage, and 13.4% had positive nodes. The sRP GS 6 10-yr metastasis-free survival, CSS, and OS were 100%, 100%, and 90% (95% CI 58-98%) respectively; pT3 and pN1 disease were found in 12% and 0%, respectively. Overall complications, high-grade complications, and severe incontinence were experienced by >50%, >10%, and >15% of men, respectively (in both the biopsy and the sRP cohorts). Limitations include the retrospective nature of the study and absence of a centralized pathological review.

Conclusions: GS 6 sRP-proven PCa recurring after nonsurgical primary treatment has almost no metastatic potential, while patients experience relevant morbidity of the procedure. However, a significant proportion of GS 6 cases at pre-sRP biopsy are upgraded at sRP. In the idea not to overtreat, efforts should be made to improve the diagnostic accuracy of pre-sRP biopsy.

Patient summary: We investigated the oncological results of salvage radical prostatectomy for recurrent prostate cancer of Gleason score (GS) 6 category. We found a very low malignant potential of GS 6 confirmed at salvage radical prostatectomy despite surgical complications being relatively high. Nonetheless, biopsy GS 6 was frequently upgraded and had less optimal oncological control. Overtreatment for recurrent GS 6 after nonsurgical first-line treatment should be avoided, and efforts should be made to increase the diagnostic accuracy of biopsies for recurrent disease.

Keywords: Gleason score 6; Prostate cancer; Recurrence; Salvage radical prostatectomy.